Dr Sean Mackey Tools To Reduce Manage Pain

High-Level Overview

Andrew Huberman talks with his Stanford colleague Dr. Sean Mackey, a physician-scientist who is chief of the Division of Pain Medicine and a professor of anesthesiology and neurology. Mackey's starting point is that pain is both a sensory and an emotional experience, one that is deeply individual and produced by the brain, not simply by an injured body part. With chronic pain affecting about 100 million Americans and costing roughly half a trillion dollars a year, he argues that society badly misunderstands what pain is. From that foundation the two build up a practical picture of pain relief: over-the-counter drugs, touch and temperature, the surprising ways pain can inhibit pain, psychology and mindfulness, nutrition and food triggers, visceral and referred pain, love, opioids and the opioid crisis, kratom and cannabis, acupuncture, chiropractic, physical therapy, supplements and national policy.

The tone is warm, candid and often funny, with Mackey sharing personal stories, from a food-poisoning episode that left him unable to eat onions to a family history of addiction that shapes his nuanced stance on opioids. The conversation moves between neuroscience, clinical practice, personal experience and public policy.

The Discussion Explores:

• Why nociception in the body is not the same as the brain's experience of pain
• How NSAIDs, aspirin and acetaminophen work, and when to use them
• Touch, gate control theory, TENS units, and the phenomenon of pain inhibiting pain
• Pain thresholds, sex differences, heat versus cold, and the role of expectations and emotion
• Distraction, mindfulness, catastrophizing and the crucial difference between hurt and harm
• Nutrition, food sensitization, visceral and referred pain, and how stress and love shape pain
• Opioids, the opioid crisis, kratom and cannabis
• Acupuncture, chiropractic, physical therapy, pacing, supplements, psychological therapies and the National Pain Strategy

Deep Dive into Main Ideas

Pain Happens in the Brain

Mackey's key message is that what happens in your injured shoulder or neck is not pain. Sensors called nociceptors in skin and deeper tissues detect heat, cold, pressure and chemical changes such as the pH shifts of inflammation. They send signals along two fiber types: fast A-delta fibers, responsible for the sharp jolt when you step on a tack, and slower C fibers, responsible for dull, achy pain. Those signals are shaped in the spinal cord and only become the experience of pain once they converge in the brain, where emotion, memory, cognition and expectation all mold them into something unique to each person.

He says Descartes' idea of a one-to-one link between stimulus and pain is wrong, yet it still lingers in the biomedical model. It leads us to project our own pain experiences onto others, which is especially harmful for people with conditions like fibromyalgia, where nothing looks outwardly wrong. There is no single pain center in the brain; the old idea of a pain matrix (insula, cingulate cortex, amygdala and more) keeps expanding, though Mackey's lab and others have found common network signatures that may serve as brain-based biomarkers of pain.

Over-the-Counter Pain Relievers

Technically, NSAIDs such as ibuprofen and naproxen are not painkillers but anti-inflammatory, anti-hyperalgesic drugs: they reduce the sensitization that follows injury rather than blocking pain from a fresh stimulus. Mackey sets the threshold for treating pain as when it interferes with quality of life, sleep, work and relationships. Because blocking inflammation may slow fracture and tissue healing, he advises the lowest effective dose, and notes that many orthopedic surgeons prefer patients avoid NSAIDs after hip or knee replacements.

There is big individual variability: ibuprofen does little for Mackey while naproxen works well. Ibuprofen is typically taken up to three times a day and naproxen twice. Take them with food and plenty of fluids, and talk to a clinician if you have stomach, bleeding, kidney or heart issues. Baby aspirin at 81 milligrams acts as an antiplatelet agent (now debated depending on age), while around 325 milligrams it behaves more like an anti-inflammatory. Caffeine touches the prostaglandin pathway and can boost pain relief, which is why it helps with headaches. Acetaminophen acts more centrally and is easy on the stomach, but the concern is the liver; he cites a limit of about 4,000 milligrams a day in divided doses for people with healthy livers who do not abuse alcohol. Prescription COX-2 inhibitors like celecoxib are gentler on the stomach.

Touch, Temperature and Pain Inhibiting Pain

Patrick Wall and Ronald Melzack's gate control theory explains why we instinctively rub or shake an injured thumb or run it under water. Touch signals travel on fast A-beta fibers and, in the spinal cord, dampen the pain signals, which Mackey calls the cheapest free version of neuromodulation ever discovered. TENS units exploit the same mechanism with a buzzing electrical stimulus. A parent's kiss on a child's scrape adds touch plus positive emotional meaning, both of which reduce pain. Studies even show that swearing reduces pain more than non-explicit exclamations.

More surprising is conditioned pain modulation: pain inhibits pain. A painful stimulus at a distant site engages brainstem circuits that send inhibitory signals down the spinal cord. First described in rodents in the late 1970s as diffuse noxious inhibitory control, it explains why a friend stomping on your foot can make your sore arm feel better, though Mackey is clear that this is not a recommendation. In some chronic pain conditions, such as fibromyalgia, this system does not work properly.

On temperature, the traditional approach is cold for the first 48 hours or so after an acute injury and heat after that. Cold reduces the release of inflammatory chemicals and slows nerve firing, while heat increases blood flow and relaxes muscles. Mackey says to use whichever works for you, within safe limits, noting that people vary a lot in whether they prefer heat or cold; he himself hates the cold and does well with heat. Numbing an area with cold is reasonable as long as you avoid frostbite, such as leaving an ice pack on for two hours.

Thresholds, Sex Differences and Context

A pain threshold is the stimulus intensity at which pain first appears. On average, men have higher heat pain thresholds than women, but Mackey stresses that people are not averages: the distributions overlap heavily, and the differences are smaller than height differences. Calling men tougher is, in his words, a terrible statement. Beliefs, expectations, anxiety, early-life trauma and context all shape the brain's interpretation. In one study, male students tolerated more heat when an attractive woman delivered the stimulus.

Thresholds can change over time through cognitive training and exercise, which likely builds up inhibitory tone. Mackey shares that with his son he tended to make light of minor injuries and laugh, since children take cues from parents, while warning that ignoring a child's real pain sends the wrong message.

Distraction, Mindfulness, Catastrophizing and Hurt Versus Harm

Mackey describes three psychological routes. Attentional distraction, such as reading, walking or time with friends and family, engages prefrontal and cingulate networks and can reduce pain significantly, but it fails at night, which is why sleep is such a problem in chronic pain. Mindful, non-judgmental acceptance of pain also works; Jon Kabat-Zinn originally developed mindfulness-based stress reduction with people who had low back pain. MBSR, everybody should do MBSR, Mackey says, adding that it helps anxiety and depression too and should be taught in schools. The third route is cognitive reframing, which underlies cognitive behavioral therapy. Each approach engages different neural circuits, and the research challenge is matching approaches to people.

He calls catastrophizing one of the biggest amplifiers of pain and predictors of poor treatment response, and names anger as another. Drawing on John Burns' work, he distinguishes anger out (loud and expressive) from anger in (simmering and contained), with data suggesting anger in is worse. Central to his practice is teaching patients the difference between hurt and harm. He recalls a master's-level tennis player who came in on crutches, depressed after months off, with a Morton's neuroma, a painful but harmless thickening around the nerves to the toes. Once told he could play, he left the crutches in the exam room. Mackey stresses that most chronic pain is more complex, but this distinction is critical. He also does not separate psychological from physical pain: it is all pain, and he treats the whole person, borrowing from more than 200 medications, including antidepressants, anti-seizure drugs and heart rhythm drugs, only a few of which are approved specifically for pain.

Nutrition, Visceral Pain and Referred Pain

Mackey calls nutrition critical and underappreciated. After food poisoning at a Mexican restaurant shortly after he turned 50, he developed severe abdominal pain and could not sleep for months. During the pandemic, eating the same foods repeatedly helped him isolate the trigger: anything in the onion family, including shallots, chives, scallions and leeks, though garlic is fine. A single exposure can bring two weeks of pain, which makes triggers hard to spot. A Stanford allergist told him she sees late-life food sensitization after an event like an infection all the time, and research suggests a gut infection can change how the gut responds to food antigens. Huberman suggests carefully done elimination diets with a food journal, gradually adding foods back.

Visceral pain from organs has broad, poorly localized receptive fields, which is why a stomachache is felt across the whole belly. Visceral and somatic signals converge in the spinal cord, producing referred pain: pelvic pain felt in the lower back, heart attack pain radiating down the left arm, and shoulder pain after abdominal surgery from irritation beneath the diaphragm. Damage to nerves themselves causes neuropathic pain, often described as shooting, stabbing, shock-like or burning, and it can be hard to treat. Mackey adds that most disc bulges, like Huberman's, are reabsorbed over time.

Stress, Memory and Love

When people report back pain or headaches that vanish on vacation or after leaving a bad job or relationship, Mackey is not surprised. The brain drives the sympathetic nervous system and cortisol, and chronic stress affects tissues, producing real pain. Early injuries can create lasting vulnerability; since a car accident at 16, stress shows up in his neck, which he takes as a signal to go work out or walk in the forest.

Positive emotion helps too. With psychologist Art Aron, who studies passionate love, and postdoc Jarred Younger, Mackey scanned people in the early, intense phase of romantic relationships while applying pain and showing them photos of their beloved, an equally attractive acquaintance, or giving them a distraction task. Love works great, he says: viewing the beloved significantly reduced pain, and the more in love people were, the greater the relief. Distraction worked about as well but through prefrontal regions, whereas love engaged reward circuits such as the nucleus accumbens and amygdala, the same circuitry involved in addiction. An unpublished follow-up hinted that brain activity during the study predicted relationship strength a year later.

Opioids and the Opioid Crisis

The body makes its own opioids, enkephalins and endorphins, and higher levels may lessen emotional reactivity. Morphine, from the poppy, was the prototype for many exogenous opioids, including oxycodone, OxyContin, fentanyl patches, tramadol, hydromorphone and methadone, which act on opioid receptors in the periphery, spinal cord and brain. Mackey, who has lost close family members to addiction, states his position plainly: I am not pro opioid. I am not anti opioid. I am pro patient. He has seen opioids transform lives and destroy them, and treats them as a tool usually reserved for later lines of care.

Opioids were overprescribed, partly because physicians get only about seven hours of pain education in medical school, compared with about 40 for veterinarians. Borrowing a framework from Stanford's Keith Humphreys, he describes most doctors as doing the right thing for the right reasons, a smaller group doing the wrong thing for the right reasons who need education, and a tiny group running pill mills who belong in jail. The fear generated by the crackdown led many doctors to abandon patients; he describes a mother cut off from a stable medication who turned to black tar heroin, and a California effort targeting prescribers that he says was followed by a doubling of deaths. Today's crisis is driven mainly by illicit fentanyl. His partner Beth Darnall's research shows that patients who want to taper can be weaned down gently and compassionately, and some find their pain improves. Benzodiazepines rarely have a role in pain.

Kratom and Cannabis

Kratom has opioid-like properties that are not fully understood. Mackey has heard the same stories as Huberman of people using it to stay off prescription or illicit opioids, and understands why it may reduce craving, much as methadone and buprenorphine do. But just because something is natural doesn't mean that it is safe, he says, pointing to rising overdose deaths associated with kratom, often alongside other substances, and unknown purity and dosing. He wants much more research and thinks it may merit being a prescribed substance.

Cannabis has reduced neuropathic pain in small, controlled studies, but larger clinic-based and population data have not shown much benefit on average. Because cannabis products vary widely in THC-to-CBD ratios and dose, he has called for moving cannabis from Schedule I to Schedule II, not to restrict it but to make it far easier to study. He believes some THC-CBD formulation will ultimately prove helpful, and mentions work by Mark Wallace at UC San Diego on specific ratios.

Acupuncture, Chiropractic, Physical Therapy and Pacing

Mackey groups chronic pain care into six categories: medications, nerve blocks and procedures, psychological and behavioral therapies, physical and occupational therapy, complementary approaches such as acupuncture and nutraceuticals, and self-empowerment through education. Combining them tends to work best. Acupuncture has scientific support, possibly via peripheral adenosine receptors and distinct brain changes compared with sham acupuncture, though the mechanism is not fully known. His advice: if you can afford the wallet biopsy, give it a try, and find a good practitioner through referrals from clinicians you trust. Medicare now covers acupuncture for some patients. Chiropractic data are mixed, and he is concerned about high-velocity neck manipulation, which carries a small risk of vertebral artery dissection, a kind of stroke. For any therapy, he asks whether it gives durable benefit or just feels good for a few hours, and he uses such therapies as a way into active rehabilitation.

Physical therapy is crucial because chronic pain leads people to withdraw, stop moving and become deconditioned. A key tool is pacing. Because chronic pain waxes and wanes, people overdo it on good days and crash, creating a boom-and-bust cycle that teaches fear of movement. Instead, set small goals, for example walking a block and then adding 50 feet the next day, stick to that limit even on great days, rest when needed on bad days, and restart the next day.

Supplements, Psychological Tools and the National Pain Strategy

For neuropathic pain, Mackey highlights acetyl-L-carnitine, which in diabetic neuropathy trials improved nerve conduction, a sign of disease modification, and alpha-lipoic acid, a free radical scavenger and T-type calcium channel modulator; he stopped taking it himself when it kept his heart rate below 150 during interval training. Vitamin C taken before certain surgeries can reduce later nerve pain, omega-3 fish oils have shown benefit in chronic pain, and small studies suggest creatine may help fibromyalgia. He warns that natural does not mean fully safe: check interactions and stop blood-thinning supplements like fish oil before surgery.

Pain psychology, he stresses, is skills training, not lying on a couch. Tools include cognitive behavioral therapy, relaxation and breathing, biofeedback, MBSR and acceptance and commitment therapy. He cites new evidence that early adverse life events alter emotional processing in adults. Beth Darnall developed Empowered Relief, a two-hour class that delivers much of what eight weeks of CBT offers, and the two are building a free digital platform to bring high-quality pain care beyond major medical centers. Mackey's one wish is full implementation of the National Pain Strategy, which he co-led with Dr. Linda Porter of the NIH and 80 experts, but which was overshadowed by the CDC opioid guidelines released around the same time. He encourages listeners to call and write their legislators, noting the strategy itself began with concerned citizens doing exactly that, and mentions his nonprofit, Pain USA.

Conclusion

Dr. Mackey's central lesson is that pain is built by the brain from body signals shaped by emotion, memory, expectation and context, which is why it differs so much from person to person and why no single fix works for everyone. That understanding opens many levers: sensible use of NSAIDs and acetaminophen, touch, heat and cold, distraction, mindfulness and reframing, knowing hurt from harm, identifying food triggers, managing stress and anger, drawing on love and connection, pacing activity, physical therapy, carefully chosen supplements and, for the right patient, opioids used thoughtfully rather than feared or dispensed freely. His pro-patient stance, emphasis on treating the whole person and push for a national strategy make this a thorough and humane guide for anyone living with pain or caring for someone who is.

This is a summary of "Dr Sean Mackey Tools To Reduce Manage Pain" from Huberman Lab, giving you the GIST so you can decide if you want the REST. Listen to the full episode.